1. Field of the Invention
The present invention relates to novel 1-arylpyrazolecarboxaldehyde oximes, compositions, and derivatives thereof. It relates to their unexpected and useful systemic insecticidal activity. The invention particularly pertains to compositions of said compounds and methods, using said compounds, for the control of arthropod, nematode, helminth or protozoan pests. In particular to the application of said compounds or compositions in agricultural methods of use, particularly as pesticides, for controlling arthropods, especially insects by systemic action. The invention also relates to 1-arylpyrazole hydrazones.
2. Description of the Related Art
The control of insects, nematodes or helminths by means of active material having a 1-arylpyrazole group therein has been described by many patents or patent application such as International Patent Publication No. WO 93/06089 (and the equivalent U.S. Pat. No. 5,451,598), WO 94/21606 and WO 87/03781 as well as in European Patent Publication Numbers 0295117, 659745, 679650, 201852 and 412849, German Patent No. DE19511269 and U.S. Pat. No. 5,232,940.
Other compounds are disclosed in WO 92/13451, Aug. 20, 1992, to Schering Agrochemicals Ltd., which describes 5-chloro-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-(4,5-dicyano-1H-imadazol-2-yl)-3-hydroxyiminomethyl-1H-pyrazole as an intermediate, also with activity against a single species Lucilia sericata, sleep blow fly.
This Schering reference appears to be the only reference describing 1-arylpyrazole-oxime compounds as insecticides.
It is an object of the present invention to provide new pesticidal compounds of the 1-arylpyrazole family together with processes for their preparation.
A second object of the present invention is to provide pesticidal compositions and pesticidal methods of use of the pesticidal pyrazole compounds against arthropods, especially insects, plant nematodes, or helminth or protozoan pests, particularly in agricultural or horticultural crops, forestry, veterinary medicine or livestock husbandry, or in public health.
A third object of the present invention is to provide very active compounds, with broad spectrum pesticidal activity, as well as compounds with selective special activity, e.g., aphicidal, miticidal, foliar insecticidal, soil insecticidal and nematicidal, systemic, antifeeding or pesticidal activity via seed treatment.
A fourth object of the present invention is to provide compounds with substantially enhanced and more rapid.activity, especially against insects and more particularly insects in their larval stages.
A fifth object of the present invention is to provide compounds with greatly improved (greater and faster) penetration into pest species when topically applied and thus provide enhanced movement of the compounds to the pesticidal site(s) of action within the pest.
Another object of the present invention is to provide compounds with high. activity and improved safety to the user and the environment.
These and other objects of the invention shall become readily apparent from the detailed description of the present invention. These objects are met in whole or in part by the instant invention.
This invention describes novel systemic chemical compositions and methods for treating plants with the compositions having insecticidal or nematocidal systemic activity of the following formula (I): 
wherein:
X is xe2x80x94S(O)mR6 or R7,
Y is hydrogen, C-3 to C-6 alkenyl, alkynyl, formyl, alkylcarbonyl, cycloalkylcarbonyl, halocycloalkyl carbonyl, aroyl, arylalkylcarbonyl, alkylsulfonyl, arylsulfonyl, haloalkylcarbonyl, aminoalkylcarbonyl, alkylaminoalkylcarbonyl, dialkylaminoalkylcarbonyl, alkoxyalkylcarbonyl, aryloxyalkylcarbonyl, alkylthioalkylcarbonyl, alkylsulfonylalkylcarbonyl, arylthioalkylcarbonyl, N-alkylcarbamoyl, N-arylcarbamoyl, N-alkylthiocarbamoyl, N-arylthiocarbamoyl, alpha-hydroxyarylalkylcarbonyl, hydroxyalkylcarbonyl, carboxyalkylcarbonyl, alkoxycarbonylalkylcarbonyl, xe2x80x94P(xe2x95x90O)(O-Alkyl)2, xe2x80x94P(xe2x95x90S)(O-alkyl)2, xe2x80x94P(xe2x95x90O)(S-alkyl)2, xe2x80x94P(xe2x95x90S)(S-alkyl)2, trialkylsilyl, alkylcarbonylaminoalkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, pyridinyl, pyrimidinyl, xe2x80x94C(xe2x95x90O)S-alkyl, xe2x80x94C(xe2x95x90O)S-aryl, xe2x80x94C(xe2x95x90O)S-alkylaryl, alkoxyalkoxycarbonyl, alkylthioalkoxycarbonyl, alkylsulfonylalkoxycarbonyl, arylthioalkoxycarbonyl, alkoxycarbonyl, aryloxycarbonyl and aryloxycarbonylalkylcarbonyl; or alkyl or haloalkyl, optionally substituted by alkoxy, alkoxycarbonyl, carboxy, cyano, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthio, nitro, alkylsulfinyl, alkylsulfonyl, alkylcarbonyl, amino, alkylamino, dialkylamino, hydroxy, alkylcarbonylamino or alkylcarbonyloxy;
Z is hydrogen, halogen, xe2x80x94C(O)R7xe2x80x94, xe2x80x94S(O)nR8, xe2x80x94C(O)OR9, alkyl, haloalkyl, xe2x80x94OR9, xe2x80x94Nxe2x95x90C(R10)(R11) alkenyl, hydrazino, alkylthiocarbonyl, 1H-pyrrol-1-yl or 1H-pyrazol-1-yl, xe2x80x94CHO, xe2x80x94CHxe2x95x90NOH, amino, R12NHxe2x80x94 or R13R14Nxe2x80x94;
R1 is hydrogen, alkyl or xe2x80x94NR15R16;
R2 is hydrogen or halogen;
R3 and R5 are hydrogen, halogen or alkyl;
R4 is halogen, haloalkyl, haloalkoxy, R17S(O)pxe2x80x94 or SF5;
R6 is alkyl or haloalkyl, alkenyl or haloalkenyl, alkynyl or haloalkynyl or cycloalkyl having 3 to 5 carbon atoms;
R7 is alkyl or haloalkyl;
R8 is R7 or phenyl;
R9 and R10 are hydrogen, alkyl or haloalkyl;
R11 is alkyl, haloalkyl, alkoxy, or a phenyl group which is optionally substituted by one or more groups selected from hydroxy, halogen, alkoxy, cyano, R7 or xe2x80x94S(O)qR7;
R12, R13 and R14, which are identical or different, are R7S(O)rxe2x80x94, formyl, alkynyl, alkoxycarbonyl, alkylthiocarbonyl or aroyl; or alkyl, C-3 to C-6 alkenyl or xe2x80x94C(O)alkyl wherein the alkyl and alkenyl portions are optionally substituted by one or more R18; or R13 and R14 are joined so as together form a divalent radical having 4 to 6 atoms in the chain, this divalent radical being alkylene, alkyleneoxyalkylene or alkyleneaminoalkylene, preferably to form a morpholine, pyrrolidine, piperidine or piperazine ring;
R15 and R16 are independently hydrogen or alkyl;
R17 represents haloalkyl;
R18 is cyano, nitro, alkoxy, haloalkoxy, xe2x80x94C(O)R7, R8S(O)sxe2x80x94, xe2x80x94C(O)OR9, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl;
m, n, p, q, r and s represent zero, one or two;
M is C-halo, Cxe2x80x94CH3, Cxe2x80x94CH2F, Cxe2x80x94CH2Cl, Cxe2x80x94NO2, or N;
geometric isomers, tautomeric forms and pesticidally active salts thereof.
By the term xe2x80x9cpesticidally acceptable saltsxe2x80x9d is meant salts the anions and cations of which are known and accepted in the art for the formation of pesticidally acceptable salts. Preferably such salts are water soluble. Suitable acid addition salts formed from compounds of formula (I) containing an amine group, include salts with inorganic acids for example hydrochlorides, phosphates, sulfates and nitrates, and salts with organic acids for example acetates. Suitable base addition salts formed from compounds of formula (I) containing a carboxylic acid group, include alkali metal (for example sodium or potassium) salts, ammonium salts and organic amine (for example diethanolamine or morpholine) salts.
Compounds of formula (I) wherein R1 represents xe2x80x94NR15R16 in which R16 represents hydrogen and R15 represents hydrogen or alkyl may exist in tautomeric forms as shown in formulae (Ia) and (Ib). Such tautomerism is well known as is described in S.Patai (The Chemistry of Functional Groups: Amidines and Imidates, Vol 2, 1991, pages 276-277). It will be understood that all such tautomeric forms are embraced by the present invention. 
Unless otherwise specified alkyl, alkoxy and alkylthio groups have from one to six (preferably one to four) carbon atoms, alkenyl groups have from two to six (preferably two to four) carbon atoms and alkynyl groups have from three to six (preferably three or four) carbon atoms. Cycloalkyl groups have from 3 to 8 carbon atoms, preferably 5 to 7 carbon atoms. By the term xe2x80x9carylxe2x80x9d is meant mono or polycyclic aromatic moieties, preferably including phenyl, pyridyl, pyrimidinyl, furyl and naphthyl groups. It shall be understood that the rings formed by the divalent alkylene radicals which include the nitrogen atoms to which they are attached are generally 5, 6 and 7 membered rings. In the instant invention, some words are used in a specific sense: The term xe2x80x9caminocarbonylxe2x80x9d means a carbamoyl radical, that is, a radical of the formula xe2x80x94C(O)NH2. Similarly, the term xe2x80x9calkylaminocarbonylxe2x80x9d means an alkylcarbamoyl radical, that is, a radical of the formula xe2x80x94C(O)xe2x80x94NH-alkyl; and the term xe2x80x9cdialkylaminocarbonylxe2x80x9d means a dialkylcarbamoyl radical, that is, a radical of the formula xe2x80x94C(O)xe2x80x94N(alkyl)2 in which the alkyl moieties can be the same or different. The term xe2x80x9caminosulfonylxe2x80x9d means a sulfamoyl radical, that is, xe2x80x94SO2NH2. Similarly, the term xe2x80x9calkylaminosulfonylxe2x80x9d means an alkylsulfamoyl radical, that is, a radical of the formula xe2x80x94SO2NH-alkyl; while the term xe2x80x9cdialkylaminosulfonylxe2x80x9d, means a dialkylsulfamoyl radical, which has the formula xe2x80x94SO2N(alkyl)2 wherein the alkyl moieties can be the same or different.
The term xe2x80x9chaloxe2x80x9d before the name of a radical means that this radical is partially or completely halogenated, that is to say, substituted by F, Cl, Br, or I, in any combination, preferably by F or Cl. The term xe2x80x9chalogenxe2x80x9d means F, Cl, Br or I. When the name of any substituent is repeated, it keeps the same meaning unless otherwise specified. The term xe2x80x9caroylxe2x80x9d designates a carbonyl aromatic radical, that is, aryl-C(O)xe2x80x94, which is preferably a benzoyl optionally substituted by one or more alkyl, alkoxy or halogen groups.
Compounds in which Z is amino, R12NHxe2x80x94 or R13R14Nxe2x80x94 are preferred.
Compounds in which X is xe2x80x94S(O)mR6 are preferred.
R1 is preferably amino or hydrogen;
R6 is preferably alkyl; especially preferred are methyl and ethyl;
R3 and R5 are preferably hydrogen;
R4 is preferably haloalkyl, haloalkoxy or SF5; especially preferred is trifluoromethyl.
M is preferably C-halo, or N.
Y is preferably hydrogen or alkoxycarbonyl.
Preferred phenyl groups or pyridyl groups comprising the R2 to R5 and M radicals in formula (I) are: 2,6-dichloro-4-trifluoromethylphenyl; 2,6-dichloro-4-trifluoromethoxyphenyl; 2-bromo-6-chloro-4-trifluoromethylphenyl; 2-bromo-6-chloro-4-trifluoromethoxyphenyl; 2,6-difluoro-4-trifluoromethylphenyl; 2-chloro-4-trifluoromethylphenyl; 3-chloro-5-trifluoromethyl-2-pyridinyl; 3-chloro-5-trifluoromethoxy-2-pyridinyl; 2-bromo-6-fluoro-4-difluoromethylphenyl; 2-chloro-6-fluoro-4-trifluoromethylphenyl; 2,6-dibromo-4-trifluoromethylphenyl; 2,6-dibromo-4-trifluoromethoxyphenyl; and 2,6-dichloro-4-pentafluorothiophenyl.
A preferred class of compounds of formula (I) are those wherein:
X is xe2x80x94S(O)mR6;
Y is hydrogen; alkyl having 1 to 4 carbon atoms (including linear, branched and cyclic) optionally substituted by aminocarbonyl, alkylsulfonyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, cyano or nitro; C-3 to C-4 alkenyl; C-3 to C-5 alkynyl; alkylcarbonyl; optionally substituted aroyl; arylalkylcarbonyl; alkylsulfonyl; alkoxycarbonylalkylcarbonyl; haloalkylcarbonyl; N-alkylcarbamoyl; alkoxycarbonyl; aryloxycarbonyl; alkoxyalkylcarbonyl; alpha-hydroxyarylalkylcarbonyl; hydroxyalkylcarbonyl; aminoalkylcarbonyl; xe2x80x94C(xe2x95x90O)S-alkyl and trialkylsilyl;
Z is amino, R12NHxe2x80x94, R13R14Nxe2x80x94, halogen or methyl;
R1 is hydrogen, methyl, amino or methylamino;
R2 is F, Cl, Br or H;
R3 and R5 are hydrogen;
R4 is CF3, CF3O, CHF2, CF3S(O)p, CF2Cl, CFCl2, CF2ClO, CFCl2O, Cl, Br, or F;
R6 is methyl or ethyl optionally substituted by F, Cl or Br;
M is CCl, CF, CBr, or N;
R12, R13 and R14 are CF3S(O)rxe2x80x94, alkynyl or alkoxycarbonyl;
or alkyl, C-3 to C-6 alkenyl or xe2x80x94C(O)alkyl wherein the alkyl and alkenyl portions are optionally substituted by one or more R18; and
R18 is cyano, nitro, alkoxy, haloalkoxy, xe2x80x94C(O)R7, R8S(O)sxe2x80x94, xe2x80x94C(O)OR9, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl or dialkylaminosulfonyl.
A further preferred class of compounds of formula (I) are those wherein:
Y represents hydrogen; a C1 to C3 alkyl group optionally substituted by cyano, carbamoyl, carboxy, alkoxycarbonyl, alkylthio, alkylsulfinyl or alkylsulfonyl; trialkylsilyl; acetyl; propionyl substituted by alkoxycarbonyl; benzoyl optionally substituted by alkyl; alkoxycarbonyl; or N-alkylcarbamoyl;
Z represents amino, R12NHxe2x80x94, R13R14Nxe2x80x94, xe2x80x94CHO, xe2x80x94CHxe2x95x90NOH, halogen or methyl;
R1 represents hydrogen, methyl, amino or methylamino;
R2 represents chlorine, bromine or hydrogen;
R3 and R5 represent hydrogen;
R4 represents CF3 or OCF3;
R6 represents optionally halogenated methyl or ethyl;
R7 represents CF3;
R12, R13 and R14 represent alkynyl; or methyl or ethyl optionally substituted by R8S(O)sxe2x80x94, cyano or aminocarbonyl;
R8 represents alkyl or phenyl; and
M represents Cxe2x80x94Cl, Cxe2x80x94Br or N.
According to another aspect of the invention, Y may be a sugar moiety, preferably Y is a ring containing 4, 5, or 6 carbon atoms and which is interrupted by one oxygen atom, the carbon atoms substituted by one or more hydroxy groups, one or more CH2OH groups or one or more OC(O)alkyl groups
The instant invention also provides arylpyrazoles of the following formula (I bis): 
wherein:
A is xe2x80x94NR26xe2x80x94;
Y1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, xe2x80x94S(O)aR28, xe2x80x94P(O)R29R30, xe2x80x94P(S)R29R30, xe2x80x94Si(R31)(R32)(R33), xe2x80x94C(O)R27, xe2x80x94C(S)R27, cyano or nitro;
R19 is hydrogen, alkyl, haloalkyl, or xe2x80x94NR34R35;
R20 is xe2x80x94S(O)bR36 or R37;
R21 is hydrogen, halogen, xe2x80x94C(O)R38, xe2x80x94S(O)cR39, alkyl, haloalkyl, xe2x80x94OR40, xe2x80x94Nxe2x95x90C(R41)(R42), alkenyl, xe2x80x94NR43R44, 1H-pyrrol-1-yl, 1H-pyrazol-1-yl, or xe2x80x94CHxe2x95x90NOH;
R22, R23 and R25 are independently selected from hydrogen, halogen or alkyl;
R24 is halogen, haloalkyl, haloalkoxy, xe2x80x94S(O)dR45 or SF5;
R26 is hydrogen or substituted or unsubstituted alkyl;
R27 is hydrogen, substituted or unsubstituted alkyl of C1 to C20, substituted or unsubstituted aryl, xe2x80x94OR46, xe2x80x94NR47R48, or xe2x80x94SR49;
R28 is substituted or unsubstituted alkyl or substituted or unsubstituted aryl;
R29 and R30 are independently selected from alkoxy and thioalkoxy;
R31, R32 and R33 are independently selected from alkyl, haloalkyl and aryl;
R34 and R35 are independently selected from hydrogen or substituted or unsubstituted alkyl;
R36 is alkyl, alkenyl, alkynyl, or C3-C6 cycloalkyl each of which is optionally substituted by one or more halogens;
R37 is alkyl or haloalkyl;
R38 is hydrogen, alkyl, haloalkyl, alkoxy or thioalkoxy;
R39 is alkyl haloalkyl or aryl;
R40 and R41 are independently selected from hydrogen, alkyl and haloalkyl;
R42 is alkyl, haloalkyl, alkoxy or phenyl each of which is optionally substituted by one or more groups selected from hydroxy, halogen, alkoxy, xe2x80x94CN, alkyl, xe2x80x94S(O)ealkyl;
R43 and R44 are independently selected from hydrogen, NH2, xe2x80x94S(O)fR50, xe2x80x94C(O)R51, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl and alkynyl; or R43 and R44 may form together a divalent alkylene radical which may be interrupted by one or more heteroatoms, preferably selected from oxygen, nitrogen and sulfur;
R45 is haloalkyl;
R46 and R49 are independently selected from substituted or unsubstituted alkyl and substituted or unsubstituted aryl;
R47 and R48 are independently selected from hydrogen, substituted or unsubstituted alkyl and substituted or unsubstituted aryl; or R47 and R48 may form together a divalent alkylene radical which may be interrupted by one or more heteroatoms preferably selected from oxygen, nitrogen and sulfur;
R50 is substituted or unsubstituted alkyl;
R51 is hydrogen, alkyl, haloalkyl, aryl, alkenyl, xe2x80x94OR52, xe2x80x94SR53, or xe2x80x94NR54R55;
R52 and R53 are independently selected from alkyl and haloalkyl;
R54 and R55 are independently selected from hydrogen, alkyl, haloalkyl and aryl;
a, b, c, d, e and f independently represent zero, one or two;
M1 is C-halo, Cxe2x80x94CH3, Cxe2x80x94CH2F, Cxe2x80x94CH2Cl, Cxe2x80x94NO2, or N;
or a pesticidally acceptable salt thereof.
A preferred group of compounds of formula (I bis) are those with one or more of the following features wherein:
A is xe2x80x94NR26xe2x80x94;
Y1 is hydrogen, alkyl, or xe2x80x94C(O)R27;
R19 is hydrogen or NH2;
R20 is xe2x80x94S(O)bR36;
R21 is xe2x80x94NR43R44;
R22 is halogen;
R23 and R25 are hydrogen;
R24 is haloalkyl;
R27 is alkyl or O-alkyl; or
M is C-halo.
Another preferred group of compounds of formula (I bis) are those wherein:
A is xe2x80x94NR26xe2x80x94;
Y1 is hydrogen, alkyl, or xe2x80x94C(O)R27;
R19 is hydrogen or NH2;
R20 is xe2x80x94S(O)bR36;
R21 is xe2x80x94NR43R44;
R22 is halogen;
R23 and R25 are hydrogen;
R24 is haloalkyl;
R27 is alkyl or O-alkyl; and
M is C-halo.
In the compounds of formula (I bis), preferably by the term xe2x80x9csubstitutedxe2x80x9d is meant by one or more of the following substituents: halogen, hydroxy, alkylthio, cyano, carboxy, xe2x80x94C(O)alkyl, xe2x80x94C(O)Oalkyl, xe2x80x94C(O)NH2, xe2x80x94C(O)NHalkyl, xe2x80x94C(O)N(alkyl)2, aryl, nitro, azido, amino, alkylamino, dialkylamino, alkylsulfenyl, alkylsulfinyl, alkylsulfonyl, aryloxy, arylthio, alkylcarbonylamino, alkylcarbonyloxy, or aryloxycarbonyl.
Among the compounds of general formula (I) or (I bis) are the following particularly preferred compounds, which provide particularly useful control of insect species by systemic action. The compound numbers are for reference purposes only.
1) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
2) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
3) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
4) 5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
5) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
6) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde oxime
7) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-difluoromethylthio-1H-pyrazole-3-carboxaldehyde oxime
8) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime
9) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylthio-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime
10) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(acetyl)oxime
11) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(2-methylbenzoyl)oxime
12) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehlyde O-(methoxycarbonyl)oxime
13) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-[2-(ethoxycarbonyl)propionyl]oxime
14) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde O-(acetyl)oxime
15) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylthio-1H-pyrazole-3-carboxaldehyde O-(methoxycarbonyl)oxime
16) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-1H-pyrazole-3-carboxaldehyde oxime
17) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(methyl)oxime
18) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(N-methylcarbamoyl)oxime
19) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(carboxymethyl)oxime
20) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
21) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(tert-butyldimethylsilyl)oxime
22) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formyl-N-hydroxy-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide
23) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-hydroxyiminomethyl-4-trifluoromethylthio-1H-pyrazole-3-carboximidamide
24) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(isopropyl)oxime
25) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(ethoxycarbonylmethyl)oxime
26) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(aminocarbonylmethyl)oxime
27) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-[2-(ethylsulfonyl)ethyl]oxime
28) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde O-(2-cyanoethyl)oxime
29) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime
30) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
31) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methyl-4-methylsulfonyl-1H-pyrazole-3-carboxaldehyde oxime
32) 5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
33) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylthio-5-methyl-1H-pyrazole-3-carboxaldehyde oxime
34) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-methyl-1H-pyrazole-3-carboxaldehyde oxime
35) 1-[2-Chloro-4-(trifluoromethyl)phenyl]-5-[2-ethylsulfonyl(ethylamino]-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
36) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-dimethylamino-4-methylthio-1H-pyrazole-3-carboxaldehyde oxime
37) 5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde oxime
38) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-pyrazole-3-carboxaldehyde oxime
39) 3-Acetyl-5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-1H-pyrazole oxime
40) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide
41) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-trifluoromethylsulfinyl-1H-pyrazole-3-carboximidamide
42) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfinyl-1H-pyrazole-3-carboximidamide
43) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylthio-1H-pyrazole-3-carboximidamide
44) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
45) 5-Amino-1-[2,6-dichloro-4-(trifluoromethoxy)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
46) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfonyl-1H-pyrazole-3-carboximidamide
47) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylthio-1H-pyrazole-3-carboximidamide
48) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-ethylsulfonyl-1H-pyrazole-3-carboximidamide
49) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
50) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-methoxy-Nxe2x80x2-methyl-4-methylsulfinyl-1H-pyrazole-3-carboximidamide:
51) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfinyl)-1H-pyrazole-3-carboximidamide
52) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-(2-fluoroethylsulfonyl)-1H-pyrazole-3-carboximidamide
53) 5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-ethylsulfinyl-1-N-hydroxy-1H-pyrazole -3-carboximidamide
54) 5-Amino-1-[3-chloro-5-(trifluoromethyl)-2-pyridinyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide
55) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-5-methylamino-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
56) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-ethylamino-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
57) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-[2-(ethysulfony)ethylamino]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
58) 5-[2-(Cyano)ethylamino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
59) 5-(Aminocarbonylmethylamino)-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-methylsulfinyl-1H-pyrazole-3-carboximidamide
60) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(phenylsulfonyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide
61) 5-Amino-1-[2,6-dibromo-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-2-N-hydroxy-1H-pyrazole-3-carboximidamide
62) 5-[2-Bromo-6-chloro-4-(trifluoromethyl)phenyl]-5-ethylamino-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide
63) 5-Amino-1-[2-bromo-6-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide
64) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide
65) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[2-(methylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide
66) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-5-[2-(ethylsulfinyl)ethylamino]-N-hydroxy-1H-pyrazole-3-carboximidamide
67) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-5-[(prop-2-ynyl)amino]-N-hydroxy-1H-pyrazole-3-carboximidamide
68) 5-Amino-1-[2-chloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-hydroxy-1H-pyrazole-3-carboximidamide.
Other compounds of formula (I) or (I bis) that are provided by the instant invention include:
69) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-amino-1H-pyrazole-3-carboximidamide;
70) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyl)amino-1H-pyrazole-3-carboximidamide;
71) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-heptylcarbonyl)amino-1H-pyrazole-3-carboximidamide;
72) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethoxycarbonyl)amino-1H-pyrazole-3-carboximidamide;
73) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-amino-1H-pyrazole carboximidamide;
74) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-amino-1H-pyrazole carboximidamide;
75) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-acetylamino-1H-pyrazole carboximidamide;
76) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-methylethenylcarbonylamino)-1H-pyrazole carboximidamide;
77) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonylamino)-1H-pyrazole carboximidamide;
78) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonylamino)-1H-pyrazole carboximidamide;
79) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonylamino)-1H-pyrazole carboximidamide;
80) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonylamino)-1H-pyrazole carboximidamide;
81) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonylamino)-1H-pyrazole carboximidamide;
82) 5-Amino-1-[2,6-dichloro-4-(trifluoronethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonylamino)-1H-pyrazole carboximidamide;
83) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonylamino)-1H-pyrazole carboximidamide;
84) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonylamino)-1H-pyrazole carboximidamide;
85) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-acetylamino-1H-pyrazole carboximidamide;
86) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-chloroacetylamino-1H-pyrazole carboximidamide;
87) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tridecylcarbonylamino)-1H-pyrazole carboximidamide;
88) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(n-propoxycarbonylamino)-1H-pyrazole carboximidamide;
89) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1,1-dimethylpropyloxycarbonylamino)-1H-pyrazole carboximidamide;
90) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tertbutyloxycarbonylamino)-1H-pyrazole carboximidamide;
91) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
92) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-ethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
93) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(ethylcarbonyloxy)-1H-pyrazole carboximidamide;
94) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(propylcarbonyloxy)-1H-pyrazole carboximidamide;
95) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(2-methylethenylcarbonyloxy)-1H-pyrazole carboximidamide;
96) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(benzoyloxy)-1H-pyrazole carboximidamide;
97) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-methylamino-4-methylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
98) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
99) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;
100) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfonyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;
101) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
102) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(heptylcarbonyloxy)-1H-pyrazole carboximidamide;
103) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-trifluoromethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
104) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfenyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
105) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(hexylcarbonyloxy)-1H-pyrazole carboximidamide;
106) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(pentylcarbonyloxy)-1H-pyrazole carboximidamide;
107) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(butylcarbonyloxy)-1H-pyrazole carboximidamide;
108) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfenyl-N-(cyclopentylcarbonyloxy)-1H-pyrazole carboximidamide;
109) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(cyclopentylcarbonyloxy)-1H-pyrazole carboximidamide;
110) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(tert-butylcarbonyloxy)-1-pyrazole carboximidamide;
111) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(isopropylcarbonyloxy)-1H-pyrazole carboximidamide;
112) 1-[2,6-Dichloro-4-(trifluoromethyl)phenyl]-5-formylamino-4-ethylsulfinyl-N-(acetyloxy)-1H-pyrazole carboximidamide;
113) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(chloroacetyloxy)-1H-pyrazole carboximidamide;
114) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(bromoacetyloxy)-1H-pyrazole carboximidamide;
115) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-(1-ethylpropylcarbonyloxy)-1H-pyrazole carboximidamide;
116) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-methylsulfinyl-N-[(3-acetyloxy)phenylcarbonyloxy]-1H-pyrazole carboximidamide;
117) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfonyl-1H-pyrazole-3-carboximidamide;
118) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-hydroxy-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboximidamide;
119) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(methoxycarbonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde hydrazone;
120) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(methylsulfonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboxaldehyde hydrazone;
121) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-ethylsulfinyl-1H-pyrazole-3-carboxaldehyde hydrazone;
122) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-trifluoromethylsulfenyl-1H-pyrazole-3-carboxaldehyde hydrazone;
123) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-amino-4-methylsulfenyl-1H-pyrazole-3-carboximidamide;
124) 5-Amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-N-(furylcarbonylamino)-4-methylsulfinyl-1H-pyrazole-3-carboximidamide; or 
Methods or Processes of Synthesis
The compounds of formula (I) can be prepared according to the manufacturing processes described in International Patent Publications Nos. WO 94/21606 and WO 93/06089 or International Patent Publication No. WO 87/03781 as well as in European Patent Publication No. 0295117 and Hatton et al U.S. Pat. No. 5,232,940. Those skilled in the art will choose the proper initial reactant in these known methods and adapt these known methods to the said reactant so as to obtain the corresponding desired products. It is understood that in the description of the following processes the sequences for the introduction of the various groups on the pyrazole ring may be performed in a different order and that suitable protecting groups may be required as will be apparent to those skilled in the art.
In the following description of processes when symbols appearing in formulae are not specifically defined, it is to be understood that they are xe2x80x9cas defined abovexe2x80x9d in accordance with the first definition of each symbol in the specification.
According to a further feature of the present invention compounds of general formula (I) wherein R2, R3, R4, R5, M, X, Y and Z are as defined above and R1 represents amino (namely compounds of formula (Ia) or (Ib) in which R15 represents hydrogen), may be prepared by the reaction of a compound of formula (II): 
with a compound of formula (III):
NH2OY
in which Y is defined above. The reaction is generally performed using an acid salt of compound (III) for example the hydrochloride salt and in the presence of a base for example pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as methanol and/or water at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein R2, R3, R4, R5, M, X, Y and Z are as defined above and R1 represents amino may be prepared by the reaction of a compound of formula (IV): 
wherein R represents alkyl, with a compound of formula (III) in which R is alkyl and Y is defined above. The reaction is generally performed using an using an acid salt of compound (III) for example the hydrochloride salt and optionally in the presence of a base for example pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as methanol and/or water at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein R2, R3, R4, R5, M, X, Y and Z are as defined above and R1 represents alkylamino or dialkylamino may be prepared by the reaction of the corresponding compound of formula (I) wherein R1 represents amino with an alkylating agent preferably of formula R-hal where R represent, alkyl and hal is chloro, bromo or iodo. The reaction is usually carried out in the presence of a strong base such as potassium t-butoxide or sodium hydride in a solvent such as tetrahydrofuran at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein R2, R3, R4, R5, M, X, Y and Z are as defined above and R1 represents hydrogen or alkyl may be prepared by the reaction of a compound of formula (V): 
in which R1 represents hydrogen or alkyl with a compound of formula (III) in which Y is defined above and using the same conditions as employed in the reaction of compounds of formula (II) with compounds of formula (III) above.
According to a further feature of the present invention compounds of general formula (I) wherein R2, R3, R4, R5, M, X and Z are as defined above, R1 represents hydrogen or alkyl, and Y is defined above with the exclusion of hydrogen, formyl, aryl, pyridinyl and pyrimidinyl (the exclusions being for chemical reasons only), may be prepared by reaction of the corresponding compound of formula (I) wherein Y represents hydrogen with an appropriate alkylating or acylating reagent or Michael acceptor generally in the presence of a base for example triethylamine in an inert solvent such as dichloroethane at a temperature of from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I) wherein Z represents R12NHxe2x80x94 or R13R14Nxe2x80x94 in which R12, R13 and/or R14 represent xe2x80x94C(O)alkyl optionally substituted by one or more R18 may be prepared by the acylation of the corresponding compound wherein Z represents amino, according to methods described in one or more of International Publications No. WO 94/21606, WO 93/06089 and WO 87/03781, European Patent Publication No. 0295117 and Hatton et al U.S. Pat. No. 5,232,940.
For the synthesis of 5-alkylamino and dialkylamino compounds wherein Z represents R12NHxe2x80x94 or R13R14Nxe2x80x94 in which R12, R13 and R14 represent alkyl or C-3 to C-6 alkenyl optionally substituted by R18, including the cyclic amino compounds (i.e., the compounds in which R13 and R14 are joined together) of formula (I), three basic methods are appropriate. The first method includes direct alkylation of precursor compounds of formula (I) in which Z represents amino with alkylating agents. The second method involves a two-step sequence, with formation of the imino ethers, followed by a reduction. The third method of preparation is through a conjugate addition, e.g., a Michael-type addition.
The compounds of formula (I) wherein Z represents R12NHxe2x80x94 or R13R14N R13 in which R12, R13 and/or R14 are R7S(O)r, formyl, alkynyl, alkoxycarbonyl, alkylthiocarbonyl or aroyl, and R7 and r are defined above can be prepared by methods described in one or more of International Publications No. WO 94/21606, WO 93/06089 and WO 87/03781, European Patent Publication No. 0295117 and Hatton et al U.S. Pat. No. 5,232,940.
The compounds of formula (I) in which Z represents hydrogen, halogen, xe2x80x94S(O)nR8, xe2x80x94C(O)R7, xe2x80x94C(O)OR9, alkyl, haloalkyl, xe2x80x94Nxe2x95x90C(R10)(R11), alkylthiocarbonyl and amino, R12NHxe2x80x94 or R13R14Nxe2x80x94 may be prepared by methods described in one or more of International Publications Numbers WO 94/21606, WO 93/06089 and WO 87/03781, European Patent Publication Numbers EP 0295117, EP 511845, EP 403309 and EP 403300, and Hatton et al U.S. Pat. No. 5,232,940, and German Patent Publication No. DE 19511269.
According to a further feature of the present invention compounds of general formula (I) wherein Z represents OR9 may be prepared by methods described in U.S. Pat. Nos. 5,047,550 and 4,918,085.
According to a further feature of the present invention compounds of formula (I) in which the substituent Z is hydrazino, 1H-pyrrol-1-yl or 1H-pyrazol-1-yl may be prepared according to the procedures described in EP 0352944. The synthesis of higher oxidation states of the compounds of formula (I), i.e., compounds in which m is 1 or 2, can be achieved by oxidation of the corresponding compounds in which m is 0 or 1.
Intermediates of formula (II) may be prepared by known methods (see for example the above listed references).
Certain compounds of formula (II) are novel and as such constitute a further feature of the invention.
Intermediates of formula (IV) wherein R represents alkyl may be prepared by the reaction of compounds of formula (II) with an alcohol of formula ROH where R is alkyl. The alcohol is usually employed in excess as the solvent but a co-solvent such as tetrahydrofuran may be present. The reaction is generally carried out in the presence of a base such as sodium alkoxide at a temperature of from 0xc2x0 C. to 100xc2x0 C.
Intermediates of formula (V) wherein R1 represents hydrogen or alkyl may be prepared by known methods for example as described in WO 8703781 and EP 295117. For example where R1 represents hydrogen by the reaction of the corresponding compound of formula (II) with diisobutylaluminium hydride, and where R1 represents alkyl by the reaction of the corresponding compound of formula (II) with an organometallic reagent of formula R1Q in which Q represents for example Mg-Cl or lithium in an inert solvent such as tetrahydrofuran.
Compounds of formula (IV) are novel and as such constitute a further feature of the invention.
Certain compounds of formula (V) are novel and as such constitute a further feature of the invention.
Intermediates of formula (III) are known or may be prepared by known methods.
According to a further feature of the present invention compounds of general formula (I bis) in which R19 is amino may be prepared by the reaction of a compound of formula (II bis): 
with a compound of formula (III bis):
H2NNR26Y1xe2x80x83xe2x80x83(III bis)
in which Y and A are defined above. The reaction is generally performed using an acid salt of A compound of formula (III bis) for example the hydrochloride salt and in the presence of a base for example pyridine or an alkali metal carbonate (such as sodium carbonate) or an alkali metal acetate (such as sodium acetate) or ammonium acetate in a solvent such as methanol and/or water at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I bis) wherein R19 is amino may be prepared by the reaction of a compound of formula (IV bis): 
wherein R represents alkyl, with a compound of formula (III bis). The reaction is generally performed using an using an acid salt of a compound of formula (III bis), for example the hydrochloride salt, and optionally in the presence of a base (for example pyridine or an alkali metal carbonate such as sodium carbonate) or an alkali metal acetate (such as sodium acetate or ammonium acetate) in a solvent such as methanol and/or water and generally at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I bis) wherein R19 represents NR34R35 and wherein one or both or of R34 and R35 are substituted or unsubstituted alkyl may be prepared by the reaction of the corresponding compound of formula (I) wherein R19 represents amino with an alkylating agent formula R-hal where R represents alkyl and hal is chloro, bromo or iodo, preferably iodo. The reaction is usually carried out in the presence of a strong base such as potassium t-butoxide or sodium hydride in a solvent such as tetrahydrofuran at a temperature from 0xc2x0 C. to 100xc2x0 C.
According to a further feature of the present invention compounds of general formula (I bis) with the above definitions wherein R19 represents hydrogen or alkyl may be prepared by the reaction of a compound of formula (V bis): 
in which R19 represents hydrogen or alkyl with a compound of formula (III bis) defined above and using the same conditions as employed in the reaction of compounds of formula (II bis) with compounds of formula (III bis) above.
According to a further feature of the invention, compounds of formula (I bis) wherein Y is xe2x80x94S(O)axe2x80x2R28, xe2x80x94P(O)R29R31, xe2x80x94P(S)R29R30, xe2x80x94Si(R31)(R32)(R33), xe2x80x94C(O)R27, xe2x80x94C(S)R27, cyano or nitro may be prepared by reaction of a compound of formula (I bis) wherein Y1 is hydrogen, with sulfenylating, sulfinylating, sulfonating phosphorylating, thiophosphorylating, silylating, acylating or thioacylating reagent, respectively, generally in the presence of a base such as triethylamine or sodium carbonate and generally in a solvent at a temperature generally in the range xe2x88x92100 to 100xc2x0 C.
According to a further feature of the invention for the synthesis of 5-alkylamino and dialkylamino compounds of formula (I bis) wherein R21 represents R43NHxe2x80x94 or R43R44Nxe2x80x94 in which R43 and R44 represent substituted or unsubstituted alkyl or substituted or unsubstituted C-3 or C-6 alkenyl three basic methods are appropriate. The first method includes direct alkylation of precursor compounds of formula (I bis) in which R21 represents amino with alkylating agents. The second method involves a two-step sequence, with formation of the imino ethers, followed by a reduction. The third method of preparation is through a conjugate addition, e.g., a Michael-type addition.
The compounds of formula (II bis) wherein R2, R3, R4, R5, R6 and M are the above described substituents can be prepared by methods described in one or more of the following: WO 94/21606, WO 93/06089, WO 87/03781, WO 97/22593; European Patent Publications EP 0295117, EP 0511845, EP 0403309, EP 0403300, EP 352944, EP 780378; U.S. Pat. Nos. 5,232,940, 5,047,550, 4,918,085; German Patent Publication No. 19511269; or by methods known to the skilled in the art.
The synthesis of higher oxidation states of the compounds of formula (I bis), i.e., compounds in which a, b, c, d, e or f are 1 or 2, can be achieved by oxidation of the corresponding compounds in which those variable are is 0 or 1.
Intermediates of formula (II bis) may be prepared by known methods (see for example the above listed references).
The compounds of TABLE 1 are illustrative of some of the preferred compounds of general formula (I) wherein R3 and R5 represent hydrogen and can be prepared by the herein described methods or processes of synthesis, by the appropriate selection of reactants, conditions and procedures, which are commonly known and apparent to one skilled in the art. In Table 1 Me means methyl, Et means ethyl and where subscripts are omitted they should be present, for example CH2 means CH2.